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Allogeneic bone marrow grafts with high levels of CD4 +CD25 +FoxP3 + T cells can lead to engraftment failure

 
: Fricke, Stephan; Rothe, Katherina; Hilger, Nadja; Ackermann, Manuela; Oelkrug, Christopher; Fricke, Christian; Schönfelder, U.; Niederwieser, D.; Emmrich, Frank; Sack, Ulrich

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Cytometry. Part A 81 (2012), No.6, pp.476-488
ISSN: 1552-4922
ISSN: 0196-4763
English
Journal Article
Fraunhofer IZI ()

Abstract
Regulatory CD4 +CD25 +FoxP3 + T cells (T regs) suppress immunological reactions. However, the effect of adding T regs to hematopoietic stem cell grafts on recovery and graft versus host disease (GvHD) is unknown. T regs from splenocytes of C57Bl/6 and Balb/c wild-type mice were isolated by MACS separation and analyzed by flow cytometry. Using a murine syngeneic transplantation model that clearly distinguishes between donor and host hematopoiesis, we showed that co-transplantation of bone marrow cells (BMCs) with high levels of T regs leads to a 100% survival of the mice and accelerates the hematopoietic recovery significantly (full donor chimerism). In allogeneic transplantation, bone marrow and T regs co-transplantation were compared to allogeneic bone marrow transplantation with or without the addition of splenocytes. Survival, leukocyte recovery, chimerism at days -2, 19, 33, and 61 for murine CD4, human CD4, HLA-DR3, murine CD3, murine CD8, murine Balb/c-H2K d, murine C57Bl/6-H2K b, and GvHD appearance were analyzed. Allogeneic bone marrow transplantation requires the addition of splenocytes to reach engraftment. Mice receiving grafts with bone marrow, splenocytes and high levels of allogeneic T regs died within 28 days (hematopoietic failure). Here, we show also detailed flow cytometric data reagarding analysis of chimerism after transplantation in unique murine hematopoietic stem cell transplantation models. Our findings showed that the syngeneic co-transplantation of CD4 +, CD25 +, FoxP3 + T-cells and BMCs induced a stimulating effect on reconstitution of hematopoiesis after irradiation. However, in the allogeneic setting the co-transplantation of T regs aggravates the engraftment of transplanted cells.

: http://publica.fraunhofer.de/documents/N-206416.html